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This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO QD on days 29-42; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; thioguanine PO QD on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive Consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO QD on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

Patients receive DI therapy comprising vincristine sulfate IV over 1 hour on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO QD on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

Patients receive IM therapy comprising vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Leucovorin Calcium

Given PO or IV

Other Names:

Adinepar

Calcifolin

Calcium (6S)-Folinate

Calcium Folinate

Calcium Leucovorin

Calfolex

Calinat

Cehafolin

Citofolin

Citrec

citrovorum factor

Cromatonbic Folinico

Dalisol

Disintox

Divical

Ecofol

Emovis

Factor, Citrovorum

Flynoken A

Folaren

Folaxin

FOLI-cell

Foliben

Folidan

Folidar

Folinac

Folinate Calcium

folinic acid

Folinic Acid Calcium Salt Pentahydrate

Folinoral

Folinvit

Foliplus

Folix

Imo

Lederfolat

Lederfolin

Leucosar

leucovorin

Rescufolin

Rescuvolin

Tonofolin

Wellcovorin

Drug: Mercaptopurine

Given PO

Other Names:

3H-Purine-6-thiol

6 MP

6 Thiohypoxanthine

6 Thiopurine

6-Mercaptopurine

6-Mercaptopurine Monohydrate

6-MP

6-Purinethiol

6-Thiopurine

6-Thioxopurine

6H-Purine-6-thione, 1,7-dihydro- (9CI)

7-Mercapto-1,3,4,6-tetrazaindene

Alti-Mercaptopurine

Azathiopurine

BW 57-323H

Flocofil

Ismipur

Leukerin

Leupurin

Mercaleukim

Mercaleukin

Mercaptina

Mercaptopurinum

Mercapurin

Mern

NCI-C04886

Puri-Nethol

Purimethol

Purine, 6-mercapto-

Purine-6-thiol (8CI)

Purine-6-thiol, monohydrate

Purinethiol

Purinethol

U-4748

WR-2785

Drug: Methotrexate

Given IT and IV

Other Names:

Abitrexate

Alpha-Methopterin

Amethopterin

Brimexate

CL 14377

CL-14377

Emtexate

Emthexat

Emthexate

Farmitrexat

Fauldexato

Folex

Folex PFS

Lantarel

Ledertrexate

Lumexon

Maxtrex

Medsatrexate

Metex

Methoblastin

Methotrexate LPF

Methotrexate Methylaminopterin

Methotrexatum

Metotrexato

Metrotex

Mexate

Mexate-AQ

MTX

Novatrex

Rheumatrex

Texate

Tremetex

Trexeron

Trixilem

WR-19039

Drug: Vincristine Sulfate

Given IV

Other Names:

Kyocristine

Leurocristine sulfate

Leurocristine, sulfate

Oncovin

Vincasar

Vincosid

Vincrex

Vincristine, sulfate

Active Comparator: Arm I (HR B-ALL M)

Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on day 1 (also day 29 of courses 1-4); prednisone PO BID on days 1-5, 29-33 (may receive methylprednisolone IV if PO is not tolerated), and 57-61; mercaptopurine PO QD on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in Arm I HR B-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

Patients receive dasatinib PO QD on days 1-56, cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32 and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15 and 22, vincristine IV over 1 minute on days 15, 22, 43 and 50, and pegaspargase IV over 1-2 hours on days 15 and 43.

DFS of children, adolescents, and young adults with very high-risk (VHR) B-ALL between arms [ Time Frame: At 4 years ]

DFS of children, adolescents, and young adults with VHR B-ALL will be compared in all arms using 1-sided log rank test, alpha 0.025.

Secondary Outcome Measures
:

Toxicity and tolerability of post-induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL [ Time Frame: Up to 10 years ]

Graded using the Version 4.0 Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI).

Toxicity and tolerability of Experimental arm and Control arm in patients with VHR B-ALL [ Time Frame: Up to 10 years ]

Graded using the Version 4.0 CTCAE of the NCI.

Increase of greater than or equal to 65% of 5-year DFS and less than 10% induction mortality in patients with Down syndrome (DS) and HR B-ALL treated with modified Induction and post-Induction therapy regimen with MBFM-IMIDM [ Time Frame: At 5 years ]

Children and young adults with Ph-like B-ALL and a predicted tyrosine kinase inhibitor (TKI)-sensitive mutation treated with dasatinib plus MBFM-IMHDM [ Time Frame: Up to 10 years ]

Toxicity and tolerability of MBFM-IMIDM in children with Down syndrome [ Time Frame: Up to 10 years ]

Graded using the Version 4.0 CTCAE of the NCI.

Percentage of VHR-ALL patients randomized to control versus experimental arms that attain MRD less than or equal to 0.01% upon recovery from consolidation [ Time Frame: Week 13-14 ]

Change in the minimal residual disease (MRD) from end-Induction to end-Consoldiation [ Time Frame: Baseline to up to 10 years ]

Whether the reduction of MRD from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arms 1 and/or 2 compared to the Control Arm will be determined.

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Ages Eligible for Study:

1 Year to 30 Years (Child, Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must be enrolled on AALL08B1 or APEC14B1 (if available for ALL patients) prior to enrollment on AALL1131

Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131

Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

Patients must have an electrocardiogram (EKG) fewer than 6 days prior to enrollment on the dasatinib arm; patients who have had cardiac assessments by echocardiogram or radionuclide scan at the beginning of induction do not need to have these repeated prior to study entry; correct QT interval (QTc) < 450 msec on baseline electrocardiogram as measured by the Frederica or Bazett formula

No major conduction abnormality (unless a cardiac pacemaker is present)

No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at sea level if there is clinical indication for determination

Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided

Patients must be aged 6 to 13 years at time of B-ALL diagnosis, enrolled on AALL1131

Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available)

Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation)

Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli

Eligibility criteria for the National Cancer Institute (NCI) standard risk patients from AALL0932 enrolling on this study at the end of Induction

Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the HR B-ALL stratum of this study at the end of Induction:

Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction:

Day 29 MRD >= 0.01%

MLL rearrangement

Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)

DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)

All patients and/or their parents or legal guardians must sign a written informed consent

All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met

Exclusion Criteria:

With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131

Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction

DS HR B-ALL patients with Induction failure or BCR-ABL1

Female patients who are pregnant are ineligible

Lactating females are not eligible unless they have agreed not to breastfeed their infant

Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained

Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation